YY1 promotes breast cancer metastasis via the DUSP6/p-ERK1/2 signaling axis 1

Background: The incidence of breast cancer (BC) and mortality from metastasis continue to increase. Yin Yang-1 (YY1) transcription factor is involved in tumor progression; however, its function in BC metastasis and its molecular mechanisms remain unclear. Methods: The expression level and prognosis of YY1 in BC were determined by bioinformatic analysis. The biological functions of YY1 were assessed on lentiviral constructs of overexpression and shRNA cell lines using wound-healing and transwell assays, and lung metastasis was observed by bioluminescence imaging of nude mice injected subcutaneously with selected cell lines. Western blotting was conducted to measure the protein levels of genes related to the extracellular signal-regulated kinase (ERK) signaling pathway and markers for the epithelial-mesenchymal transition (EMT). The binding of YY1 to the promoter of dual specificity phosphatase 6 (DUSP6) was evaluated by means of a luciferase reporter gene assay. Results: In BC tissues, YY1 is expressed at a high level, and a higher expression level of YY1 is linked to the N and M stages and a worse prognosis. YY1 promotes the invasion, migration, and EMT of BC cells both in vitro and in vivo. This is the first study of BC to show how YY1 binds to the DUSP6 promoter and represses its transcription, thus activating the ERK pathway to promote EMT and BC progression. Conclusions: As an oncogene, YY1 promotes BC metastasis by targeting DUSP6 to activate the ERK pathway. For patients with BC, it could serve as a novel treatment target.